Modeling the impact of high-dose versus standard-dose influenza vaccines on strength and breadth of the antibody response

Introduction

• Influenza vaccines are good, but could be better.
• The vaccine is especially sub-par in older adults.
• Enhanced vaccines are now recommended for older adults.
• One enhancement is to use a higher dose of antigen: Fluzone High-Dose (HD) versus Fluzone Standard-Dose (SD).

Motivation

• Fluzone HD is more immunogenic compared to Fluzone SD for the strains contained in the vaccine.
• Unclear if Fluzone HD also induces a broader antibody response against other/heterologous strains.

Motivation

• We explored the impact of dose on antibody breadth (and strength) using data from a vaccine cohort.

SD versus HD vaccine study

All individuals >=65y

Billings et al 2025 JID

Vaccine Strains

“Raw” data - homologous responses

“Raw” data - heterologous responses

The model (brms code)

Bayesian, hierarchical model. Nesting of strains/individuals/seasons.

See paper supplement for all the math.

H1N1 antibodies after HD/SD vaccine

H3N2 antibodies after HD/SD vaccine

Overall strain-specific response

Overall season response

Conclusions

• Overall, the HD vaccine seems to induce a somewhat better response compared to the SD vaccine.
• The effect is not strong, and varies by vaccine strain/season.
• It might be worth to further tweak/increase the dose.

Acknowledgements

• Other co-authors, NIH
• Slides: https://www.andreashandel.com/presentations/